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Purpose/Objective: The optimal radiotherapy strategy for prostate cancer (PC) patients with high nodal risk remains debated. This prospective phase II study reports long‑term clinical outcomes, toxicity, and patient‑reported outcomes in men with PC treated with whole‑pelvis radiotherapy and dose escalation to MRI‑identified intraprostatic lesions and PET‑positive pelvic lymph nodes.

Materials/Methods: Eighty‑five PC patients with high nodal risk or up to three pelvic nodal metastases were enrolled between 2013 and 2017. Radiotherapy delivered 77 Gy to the prostate and 56 Gy to pelvic nodes in 35 fractions, with escalation to 70 Gy for PET‑positive nodes and 84 Gy for MRI‑defined intraprostatic lesions when feasible. Endpoints included biochemical progression‑free survival, overall survival, toxicity, and longitudinal patient‑reported outcomes.

Results: Seventy-eight patients underwent radiotherapy. Of these, 42 received an intraprostatic boost and were classified as the per-protocol population. Median follow‑up was 7.8 years, and 26% had N1 disease. For the full cohort, five‑year biochemical progression‑free survival was 76%, with poorer results among patients with RECIST‑positive nodal involvement. Five‑year overall survival was 95%. Acute grade ≥ 2 genitourinary and gastrointestinal toxicities occurred in 33 and 23%, respectively, and decreased over time. No grade ≥ 3 gastrointestinal toxicity was observed. Patient‑reported outcomes showed low long‑term urinary and bowel bother.

Conclusion: Whole‑pelvis radiotherapy with targeted dose escalation was well tolerated. The high proportion of patients not receiving an intraprostatic boost underscores methodological challenges and emphasises the need for standardised imaging interpretation and delineation guidelines.